Long-term Extension Study of Apremilast in Pediatric Patients Aged 6-17 with Moderate to Severe Plaque Psoriasis

The primary objective of this study is to evaluate the **long-term safety** of apremilast in pediatric patients aged 6 to 17 years with moderate to severe plaque psoriasis. This is clinically relevant as it aims to ensure the safety profile of apremilast, a treatment option for this chronic dermatological condition, over an extended period in a younger population.

Secondary objectives include:

• Evaluating the maintenance of effect as measured by static Physician Global Assessment (sPGA).

The clinical trial involves a total of **71 participants** diagnosed with **moderate to severe plaque psoriasis**. The study population comprises both male and female subjects aged between 6 and 17 years. Participants were selected based on specific criteria, including a minimum weight of 20 kg and a body mass index (BMI) no lower than the 5th percentile according to the Centers for Disease Control (CDC) growth chart for children and adolescents. The trial focuses on evaluating the long-term safety of apremilast in this demographic. Participants are required to have completed the Apremilast Extension Phase of a previous study (Study CC-10004-PPSO-003). The trial includes a vulnerable population, as it involves children and adolescents. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a Phase 3B, multi-center, open-label, long-term extension study designed to evaluate the long-term safety of **apremilast** in pediatric subjects aged 6 through 17 years with moderate to severe plaque psoriasis. The trial is not randomized or double-blind, as it follows an open-label design, allowing all participants to receive the investigational medicinal product, Otezla, in the form of film-coated tablets. The trial is expected to span from December 18, 2019, to February 16, 2027, with a maximum treatment period of 208 weeks for each participant.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, weight, and completion of a prior study phase. Following the screening, participants will attend regular follow-up visits to monitor safety and efficacy endpoints. These visits will include assessments of adverse events, depression, suicidal thoughts, and behavior using the Columbia-Suicide Severity Rating Scale (C-SSRS), as well as Tanner Staging for sexual maturity. Growth parameters such as body weight, height, and BMI will be measured at each visit. The study will conclude with an end-of-study visit, where final assessments will be conducted.

The expected length of participant involvement is up to 208 weeks, contingent upon continued eligibility and adherence to study protocols. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or withdrawal of consent by the participant or their legal guardian. The primary endpoints focus on the type, frequency, severity, and relationship of adverse events to apremilast, while secondary endpoints include the proportion of subjects achieving a specific score on the static Physician's Global Assessment (sPGA).

The clinical trial involves the administration of **Otezla** (apremilast) in the form of film-coated tablets, available in dosages of 10 mg, 20 mg, and 30 mg. The tablets are intended for **oral use**. The maximum daily dose is 60 mg, with a total maximum dose of 87,360 mg over the course of the study. The treatment period extends up to 208 weeks. The investigational medicinal product (IMP) is manufactured using the same process as the commercial product but is specifically packaged and labeled for clinical trial use. The pharmaceutical form is consistent with standard film-coated tablets, ensuring ease of administration and compliance monitoring.

In this study, no non-experimental treatments such as placebo or comparator treatments are utilized. The focus is solely on evaluating the long-term safety of apremilast in pediatric subjects aged 6 through 17 years with moderate to severe plaque psoriasis. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The study is designed to provide comprehensive safety data for the use of apremilast in the specified patient population.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the evaluation of **adverse events** in terms of type, frequency, severity, and their relationship to apremilast from Week 0 through the end of the observational follow-up. Additionally, the Columbia-Suicide Severity Rating Scale (C-SSRS) Questionnaire will be utilized to monitor depression, suicidal thoughts, and behavior throughout the study duration. Tanner Staging will be assessed at Week 0 and every 52 weeks thereafter, including at early termination visits, to evaluate sexual maturity. Growth will be monitored by measuring body weight, height, and BMI at each visit.

The secondary endpoint involves the Static Physician's Global Assessment (sPGA), where the proportion of subjects achieving a score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline will be determined. These efficacy parameters will be collected and analyzed at specified timepoints to ensure comprehensive evaluation of the treatment's impact on moderate to severe plaque psoriasis in pediatric subjects aged 6 through 17 years.